Treatment medium delivery device and methods for delivery of such treatment mediums to the eye using such delivery device

ABSTRACT

A device for delivering a treatment medium to an eye includes a first body portion configured to be removably inserted and secured in an opening of the eye, and a second body portion supported by the first body portion. At least the second body portion includes a treatment medium, and a coating having an opening through which the treatment medium elutes out of the device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 13/081,865, filed 7 Apr. 2011, which is acontinuation of U.S. patent application Ser. No. 11/571,147, filed Dec.21, 2006, which was the United States National Phase entry ofInternational Patent Application No. PCT/US05/23848, filed Jul. 1, 2005,which claims the benefit of priority from U.S. Provisional PatentApplication Ser. No. 60/585,287, filed Jul. 2, 2004. The contents of allare incorporated herein by reference in their entireties.

FIELD OF INVENTION

The present invention relates to methods, devices and techniques fortreating eyes, such as eyes of mammals having eye disorders or diseases,more particularly to methods, devices and techniques for delivery of oradministering a therapeutic medium/agent or other treatment medium tothe eye and more particularly a medium delivery device being disposed ina punctum of an eye and methods related thereto. Also featured aremethods related thereto for treating eyes using such treatment mediumdelivery devices and prophylactic administration of such therapeutics orother treatment mediums to eyes.

BACKGROUND OF THE INVENTION

There are a number of surgical procedures for the eye in which atherapeutic medium is instilled postoperatively in or on the eye as wellas a number of therapeutic or treatment procedures in which atherapeutic medium or another medium or fluid is instilled on the eyetopically. For example, for Lasik, cataract and other refractiveprocedures anti-inflammatories such as-steroids and anti-infective drugsare topically administered post-operatively. Also, the treatment ofcorneal diseases such as corneal melts or post-operative management ofcorneal transplants also can involve the topical delivery of drugs tothe eye. Further, drugs or therapeutic mediums are delivered topicallyfor the treatment of inflammatory eye disorders or eye infectiousdisorders.

In addition to the administering of drugs postoperatively and/orprophylactic administration for treatment of eye disorders or diseases,there also can arise a need to maintain a desired level of moisturepostoperatively as well for treating what is commonly referred to as dryeye over a short period or long period of time. With reference to FIG.1, the lacrimal glands continuously secrete tears that bathe the corneaand conjunctiva of the eye that moisten these tissues as well providinga vehicle for removing or washing away foreign substances (e.g.,particles) that alight on the external surface (e.g., conjunctiva) ofthe eye. As the tears being secreted drain from the eye through thenasolacrimal duct, the drainage of the tears may make it difficult toachieve the desired level of moisture. It also is possible that theamount of fluid that can be secreted is insufficient for achieving thedesired level of moisture such as that which occurs with the dry eyecondition.

There exist a wide range of procedures or techniques for accomplishingsuch treatment. In one technique, plugs, sometimes referred to aspunctum plugs are inserted using appropriate medicaltechniques/procedures into at least one of the two punctums of theaffected or given eye. The inserted plug occludes the at least onepunctum thereby preventing the flow of any tears or fluid through theoccluded punctum, to the tear drainage ducts (upper lacrimal canaliculusand lower lacrimal canaliculus) and thus through the nasolacrimal duct.With such plugging of a punctum, the tears or fluid being secreted donot easily drain from the eye and thus are retained in the eye. This isso because the secreted tears only can escape the eye either by flowingthrough the punctum that is not plugged or by the tears or fluidoverflowing and exiting the eye such as that seen when one cries. Inother techniques, the individual directly administers or topicallyadministers artificial tears, restasis, allergan or other agents to thetreatment the drying eye condition.

Treatment of ophthalmic conditions using drugs applied directly to theeye in either liquid or ointment form, (i.e., topical administration) isgenerally effective for treating problems involving the superficialsurface of the eye and diseases that involve the cornea and anteriorsegment of the eye, such as for example, conjunctivitis. As indicatedabove, however, such topical eye drops, however, can drain from the eyethrough the nasolacrimal duct and into the systemic circulation. As aconsequence, the medication available for treatment is thus diluted orreduced and the drainage also increases the risk of unwanted systemicside effects. Further, data also indicates that it is not unusual for upto 85% of topically applied agents to be removed by the eye's blinkmechanism/reflex. In addition the conventional technique of deliveringdrugs in the form of topical eye drops is of little utility because thedrug can be highly unstable and therefore not easily formulated fortopical delivery.

The use of a topical insert for direct delivery of drugs to the eye hasbeen contemplated/attempted, however, this method has been found not tobe desirable as such conventional topical inserts typically requirepatient self-administration and thus education on their insertion intoand removal from the eye. Consequently, this particular techniquedemands a certain degree of manual dexterity that can be problematic forgeriatric patients who are particularly susceptible to certain eyedisorders that appear age related. Also, in many instances such topicalinserts may cause eye irritation and such conventional inserts are proneto inadvertent loss due to eyelid laxity. Further, as with topicaladministration techniques described above, the drug being delivered bysuch a topical inset is drained from the eye through the nasolacrimalduct and into the systemic circulation, thereby diluting or reducing theamount of the drug that is available for treatment and the drainage alsoincreases the risk of unwanted systemic side effects. Thus, suchconventional direct delivery devices have limited, if any at all,utility for providing an effective source of drugs.

It thus would be desirable to provide a new device that provides a moreeffective pathway for controlled, direct delivery or administration ofdrugs, therapeutic mediums or other treatment mediums to the eye as wellas providing new methods, for delivery of such drugs, therapeuticmediums or other treatment mediums (e.g., artificial tears) to the eyeusing such devices. It would be particularly desirable to provide such adevice and method that would be more effective in delivering the mediumtopically as well as being retained within the eye in comparison to theprior art technique of direct delivery of the treatment medium/drug. Italso would be desirable to provide such a device that can be adapted todelivery any of a number of drugs, therapeutic mediums, or othertreatment mediums without changing the basic delivery concept. It alsowould be desirable to provide such a device that is adapted forremovable insertion into an exiting bodily orifice of the eye, thepunctum, whereby the device is retained there during normal eye activityas compared to prior art devices. It also would be desirable to providea device that is adapted to provide a controllably releasable source ofdrugs, therapeutic medium or other treatment medium for administrationover a desired period of time as compared to existing topicaladministration techniques.

SUMMARY OF THE INVENTION

The present invention features a device for delivering a treatmentmedium to an eye as well as methods related thereto. Such devices andmethods allow a desired amount of the treatment medium to be deliveredin a controllable manner over a predetermined time period directly tothe eye. Such devices preferably are such as to allow medical personnelto localize the device to a delivery site within the eye (e.g., within anatural opening or orifice of the eye) for delivery of the treatmentmedium and removal by such medical personnel following such a treatmentprocess.

In more particular embodiments, the delivery device is configured andarranged so that the treatment medium is eluted from one portion of thedelivery device, thereby controllably delivering a desired amount of thetreatment medium to the eye. In addition, the delivery device also isconfigured and arranged so that another portion thereof is removablysecured within a natural opening or orifice in or proximal to the eye.In specific embodiments the another portion is configured and arrangedso as to be removably secured within the natural opening comprising atleast one punctum of an eye.

In further embodiments, the delivery device is configured and arrangedsuch that when a delivery device is removably inserted into the one orboth punctums, the delivery device occludes or plugs each punctum.Consequently, tears being secreted and/or the treatment medium beingeluted from the delivery device is prevented from draining through theplugged punctum(s) and thus to the tear drainage ducts. This therebynecessarily increases the retention time of the treatment mediumproximal the exterior surface of the eye as compared to conventionaltechniques. This increased retention time also necessarily provides amechanism by which the treatment medium can traverse the barrier formedby such external surfaces such that the treatment medium can bedelivered to other portions of the eye, for example, the anteriorsegment or portion of the eye.

In further embodiments the another portion of the delivery deviceembodies any of a number of techniques known to those skilled in the artfor the controlled release of a treatment medium there from. In morespecific embodiments, said another portion comprises a coating that isapplied to an end segment of the delivery device first portion, whichcoating is configured or arranged so the treatment medium iscontrollably released there from. In further embodiments, the anotherportion of the delivery device embodies a sustained release device orstructure whereby the treatment medium is eluted or diffused there fromas well as structures whereby the treatment medium traverses thesupporting/protecting structure via other known techniques such asosmosis.

In further embodiments, the delivery device first portion comprises astent, plug type member or a coil member; one end of which is configuredand arranged so as to be removably secured within the natural opening,more specifically the punctum. The other end of which is configured andarranged so as to form a structure to which is secured and/or appliedthe coating or member from which the treatment medium is controllablereleased. In specific embodiments, the stent, plug type member or coilmember comprises a backbone, platform or support member to which thetreatment medium coating is applied or to which the treatment mediummember is secured.

In further embodiments, the treatment medium comprises mediums or agentsin what ever form that are useable in connection with, but not limitedto, the treatment of a wide range of disorders, diseases, and/orphysiological problems of a mammalian eye. Such treatment mediums of thepresent invention in what ever form also are useable in connection withsurgical procedures. Such treatment mediums include but are not limitedto therapeutics and medicaments. Exemplary therapeutic mediums include,but are not limited to, thrombin inhibitors; antithrombogenic agents;thrombolytic agents; fibrinolytic agents; vasospasm inhibitors; calciumchannel blockers; vasodilators; antihypertensive agents; antimicrobialagents, such as antibiotics (such as tetracycline, chlortetracycline,bacitracin, neomycin, polymyxin, gramicidin, cephalexin,oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin,gentamycin, erythromycin, penicillin, sulfonamides, sulfadiazine,sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodiumpropionate), antifungals (such as amphotericin B and miconazole), andantivirals (such as idoxuridine trifluorothymidine, acyclovir,gancyclovir, interferon); inhibitors of surface glycoprotein receptors;antiplatelet agents; antimitotics; microtubule inhibitors;anti-secretory agents; active inhibitors; remodeling inhibitors;antisense nucleotides; anti-metabolites; antiproliferatives (includingantiangiogenesis agents); anticancer chemotherapeutic agents;anti-inflammatories (such as hydrocortisone, hydrocortisone acetate,dexamethasone 21-phosphate, fluocinolone, medrysone, methylprednisolone,prednisolone 21-phosphate, prednisolone acetate, fluoromethalone,betamethasone, triamcinolone, triamcinolone acetonide); non-steroidalanti-inflammatories (such as salicylate, indomethacin, ibuprofen,diclofenac, flurbiprofen, piroxicam); antiallergenics (such as sodiumchromoglycate, antazoline, methapyriline, chlorpheniramine, cetrizine,pyrilamine, prophenpyridamine); anti-proliferative agents (such as1,3-cis retinoic acid); decongestants (such as phenylephrine,naphazoline, tetrahydrazoline); miotics and anti-cholinesterase (such aspilocarpine, salicylate, carbachol, acetylcholine chloride,physostigmine, eserine, diisopropyl fluorophosphate, phospholine iodine,demecarium bromide); antineoplastics (such as carmustine, cisplatin,fluorouracil); immunological drugs (such as vaccines and immunestimulants); hormonal agents (such as estrogens, estradiol,progestational, progesterone, insulin, calcitonin, parathyroid hormone,peptide and vasopressin hypothalamus releasing factor);immunosuppressive agents, growth hormone antagonists, growth factors(such as epidermal growth factor, fibroblast growth factor, plateletderived growth factor, transforming growth factor beta, somatotropin,fibronectin); inhibitors of angiogenesis (such as angiostatin,anecortave acetate, thrombospondin, anti-VEGF antibody.); dopamineagonists; radiotherapeutic agents; peptides; proteins; enzymes;extracellular matrix components; ACE inhibitors; free radicalscavengers; chelators; antioxidants; anti-polymerases; photodynamictherapy agents; gene therapy agents; and other therapeutic agents suchas prostaglandins, antiprostaglandin, prostaglandin precursors, and thelike.

Antiproliferatives include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art thatinhibit the proliferation of cells. Such compounds, agents, therapeuticmediums or drugs include, but are not limited to, 5-fluorouracil, taxol,rapamycin, mitomycin C and cisplatin.

Neuroprotectives include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art thatguard or protect against neurotoxicity; the quality of exerting adestructive or poisonous effect upon nerve tissue. Such compounds,agents, therapeutic mediums or drugs include, but are not limited to,lubezole.

Anti-inflammatories include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art, eithersteroidal or non-steroidal, and generally characterized has having theproperty of counteracting or suppressing the inflammatory process.Non-steroidal inflammatory drugs or compounds comprise a class of drugsthat shares the property of being analgesic, antipyretic andanti-inflammatory by way of interfering with the synthesis ofprostaglandins. Such non-steroidal anti-inflammatories include, but arenot limited to, indomethacin, ibuprofen, naxopren, piroxicam andnabumetone. Such anti-inflammatory steroids contemplated for use in themethodology of the present invention, include triamcinolone acetonide(generic name) and corticosteroids that include, for example,triamcinolone, dexamethasone, fluocinolone, cortisone, prednisolone,flumetholone, and derivatives thereof (See also U.S. Pat. No. 5,770,589,the teachings of which are incorporated herein by reference).

As is known to those skilled in the art, growth factors is a collectiveterm originally used to refer to substances that promote cell growth andis now loosely used to describe molecules that function as growthstimulators (mitogens) but also as growth inhibitors (sometimes referredto as negative growth factors), factors that stimulate cell migration,or as chemotactic agents or inhibit cell migration or invasion of tumorcells, factors that modulate differentiated functions of cells, factorsinvolved in apoptosis, factors involved in angiogenesis, or factors thatpromote survival of cells without influencing growth anddifferentiation. In the present invention, such growth factors include,but are not limited to, pigment epithelium derived factor and basicfibroblast growth factor.

As is known to those skilled in the art, neurotropic factors is ageneral term used to describe growth factors and cytokines that canenhance neuronal survival and axonal growth and that regulate synapticdevelopment and plasticity in the nervous system. In the presentinvention, such growth factors include, but are not limited to, ciliaryneurotrophic factors and brain-derived neurotrophic factors.

Antiangiogenics include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art thatinhibit the growth and production of blood vessels, includingcapillaries. Such compounds, agents, therapeutic mediums or drugsinclude, but are not limited to, anecortave acetate and anti VEGFantibody.

Thrombolytics, as is known to those skilled in the art include any of anumber of compounds, agents, therapeutic mediums or drugs that dissolveblot clots, or dissolve or split up a thrombus. Such thrombolyticsinclude, but are not limited to, streptokinase, tissue plasminogenactivator or TPA and urokinase.

Such treatment mediums also include fluticasone.

The treatment medium including therapeutics being delivered oradministered is in any of a number of formulations including fluidsolutions, solids and/or sustained release formulations or devices. Infurther embodiments, the sustained releases devices comprising saidanother portion of the delivery device of the present invention include,but are not limited to those having the following characteristics;flexible rods, thin films, foldable discs, biodegradable polymers withthe therapeutic medium (e.g., drug) embedded within, drug elutingpolymer coatings over a rigid scaffold, compressed drug “pellets” or atherapeutic medium encapsulated in a semi-permeable membrane. Also, somecharacteristic formulations for delivery of the treatment mediuminclude, but are not limited to, injectable hydrogels, cyclodextrin“solubilized” and micronized solutions.

The another portion of the delivery device of the present invention cancomprise a biocompatible capsules suitable for delivery of thetherapeutic medium. Exemplary biocompatible polymer capsulescontemplated for use in the methodology of the present inventioncomprise (a) a core or compartment which contains the therapeuticmedium, either suspended in a liquid medium or immobilized within abiocompatible matrix, and (b) a surrounding jacket comprising a membranethat is biocompatible and permits diffusion of the drugs, therapeutics,medicaments such as proteins, cells or small molecule pharmaceuticals,or the like to the tissues of the eye. As indicated herein, thecompartment can comprise a biocompatible matrix of a hydrogel or otherbiocompatible matrix material that stabilizes the position of thetherapeutic medium. The jacket for the capsule may be manufactured fromvarious polymers and polymer blends including polyacrylates (includingacrylic copolymers), polyvinylidenes, polyvinyl chloride copolymers,polyurethanes, polystyrenes, polyamides, cellulose acetates, cellulosenitrates, polysulfones (including polyether sulfones), polyphosphazenes,polyacrylonitriles, poly(acrylonitrile/covinyl chloride), as well asderivatives, copolymers, and mixtures thereof.

Methods according to the present invention include, but are not limitedto pre-/post-operative treatment procedures in which a delivery deviceof the present invention is inserted into orifice or opening in the eye(e.g., punctum) prior to, during or subsequent to treatment medium priorto, during and/or subsequent to the operative/surgical procedure suchthat the treatment medium is dispensed prior to, during and/orsubsequent to the surgical procedure. It also is contemplated that suchmethods includes inserting a plurality or more delivery devices atdifferent times (e.g., before and during the surgical procedure) so thetreatment medium can be appropriately set and/or adjusted to meet theparticular needs of a given phase of the treatment process. Also, suchmethods contemplate inserting a plurality or more delivery devices atdifferent times to adjust and control the constitution of the treatmentmedium to accommodate changing medical needs. For example, the treatmentregime and thus the treatment medium may need to be changed to dispensean antibiotic or other therapeutic medium because of the presence of aninfection or other medical condition (inflammation).

In addition, the methods of the present invention contemplate insertionof a delivery device in non-surgical cases, for treatment of aphysiological condition, disease condition (e.g., infectious problem) orother condition of the eye (e.g., inflammatory disorders) treated byadministering medicaments, therapeutics and the like. It also iscontemplated that such methods includes inserting a plurality or moredelivery devices at different times throughout the treatment regime orprocess so the treatment medium provided for administration can beappropriately set and/or adjusted to meet the particular needs of agiven phase of the treatment process or regime. Thus, the medicalpersonnel would remove the delivery device presently inserted in theopening and insert in its place another delivery device having adifferent constitution that the presently inserted device or to replacea spent or used up delivery device with a fresh delivery device.

In addition, to treatment of diseased eye conditions and or use inconjunction with surgical procedures, the methods of the presentinvention also contemplate insertion of a delivery device forprophylactic administration of a treatment medium over a short or longperiod of time. The methods of the present invention also contemplateadministration of a treatment medium to the eye for prophylactictreatment of a physiological condition of an eye(s) such as for example,the treatment of the so-called dry-eye condition.

Also featured are systems embodying such delivery devices as wellmethods implementing the techniques and processes embodied in suchdelivery devices.

Other aspects and embodiments of the invention are discussed below.

BRIEF DESCRIPTION OF THE DRAWINGS

For a fuller understanding of the nature and desired objects of thepresent invention, reference is made to the following detaileddescription taken in conjunction with the accompanying drawing figureswherein like reference character denote corresponding parts throughoutthe several views and wherein:

FIG. 1 is an illustrative view of an eye;

FIG. 2A is a schematic view illustrating a treatment medium deliverydevice according to a first embodiment of the present invention;

FIG. 2B is a schematic view illustrating a treatment medium deliverydevice according to a second embodiment of the present invention;

FIG. 2C is a schematic view illustrating a treatment medium deliverydevice according to a third embodiment of the present invention;

FIG. 2D is a schematic view illustrating a treatment medium deliverydevice according to a fourth embodiment of the present invention;

FIG. 3A is a partial view of a first body portion of the presentinvention illustrating an example configuration of an end thereof;

FIG. 3B is a partial view of a first body portion of the presentinvention illustrating another example configuration of an end thereof;

FIG. 4 is a schematic view of a second body portion according to anembodiment of the present invention; and

FIGS. 5 and 6 are various view of an eye showing insertion of atreatment delivery device according to the present invention in thepunctum.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the various drawing figures wherein like referencecharacters refer to like parts, there is shown in FIG. 2A a treatmentmedium delivery device 100 according to the present invention includinga first body portion 110 and a second body portion 120. The second bodyportion 120 is generally configured and arranged so as to include thetreatment medium that is to be dispensed to the exterior surface of aneye 2 (FIGS. 1, 5, and 6) being treated, the exterior surface includesbut is not limited to the cornea and conjunctiva.

The first body portion 110 is sized, configured and arranged so as to beremovably inserted, and secured in an opening provided in the eye, moreparticularly, a portion of the body proximal the eye. More particularly,the first body portion 110 is sized, configured and arranged such thatwhen the first body portion is inserted into the opening it is securedwithin the opening so it does not fall or come out as a result of normaland expected bodily function, such as for example, blinking of theeyelids and any laxity of the eye. In particular exemplary embodiments,the opening in the eye is a punctum 4 (FIGS. 1, 5, and 6) of the eye 2for a mammalian body that is fluidly coupled to a lacrimal canaliculus 6(FIGS. 1, 5, and 6) and the treatment medium delivery device of thepresent invention is configured and arranged so it remains securedwithin the punctum and a portion of the lacrimal canaliculus duringnormal eye function.

The first body portion 110 is configurable as a solid member, a memberhaving a lumen or passage defined therein, a member having a passagepassing through a portion of the first body portion, an open compartmentlocated within the first body portion or a body structure thatcorresponds in great part to the structure of a conventional stent (seeFIG. 2D). As is known to those skilled in the art, a stent provides ascaffold like structure that can be arranged to form a generallycylindrical shape or a shape that conforms to the opening and passagethe stent is being inserted into. The term “stent,” as used herein,includes any scaffold like structures as well as conventional stents.The first body portion 110 also is constructed of any of a number ofbiocompatible materials as is known to those skilled in the art,including metals such as stainless steel and nitinol (nickel-titanium)and plastics that have strength and material characteristics suitablefor the intended use. Such materials of the first body portion 110 alsopreferably are characterized as being non-toxic and non-sensitizing.

Such a first body portion 110 also is sized and arranged so that medicalpersonnel can grasp the delivery device 100 using any of a number ofmedical instruments (e.g., forceps, clamp) and to manipulate the firstbody portion 110 so it is inserted into the opening without causing thefirst body portion to break or to deform during such insertion to theextent that it would prevent removal of the first body portion from theopening. Such a first body portion 110 also is sized and arranged so themedical personnel can grasp the delivery device 100 at a later timethereby allowing the delivery device, more particularly the insertedpart of the first body portion to be removed or extracted from theopening without structural failure. Preferably such insertion andextraction also is accomplished without causing significant injury tothe tissues of the opening about and proximal to the entry site thereof.

In more particular embodiments, the first body portion includes an end112 that is configured to facilitate insertion of the first body portion110 into the opening as well as to minimize significant trauma and/orinjury to the tissue of the opening as the first body portion is beinginserted therein. In specific exemplary embodiments, the first bodyportion end 112 is arcuate and/or generally hemispherical. It iscontemplated and within the scope of the present invention for the firstbody portion end 112 to be configured so it presents an end that isappropriate for the intended function and use. For example, the end 112is configurable so as to have a piercing capability if the function anduse of the first end portion 110 would involve piercing of tissue or amembrane as the first portion end is being inserted into the bodyopening.

In further embodiments, a second end 114 of the first body portion 110is arranged so as to form a platform, structure, scaffold or support forthe second body portion 120. As such the first body portion second end114 is configurable so as to form any of a number of arrangements orconfigurations suitable for the use/application. With reference also toFIGS. 3A, B; such arrangements for the first body portion second ends114, 114 a, 114 b, include, but are not limited to; an extension of thefirst body portion 110 (as illustrated in FIG. 2A), a rod 115 extendingfrom a surface of the first body portion 110 a (as illustrated in FIG.3A), a plurality of rods 115 a-c extending from a surface of the firstbody portion 110 b (as illustrated in FIG. 3B) or one or more outwardlyextending elements of any geometric cross-section; where each of therods and/or outwardly extending elements having a cross-section smallerthan the cross-section or diameter of the first body portion.

In an embodiment of the present invention, the second body portion 120comprises a member, device (e.g., an eluting device, a sustainedreleased device, an encapsulation device) or coating that is applied,secured, attached or bonded to the first body portion second end 114using any of a number of techniques known to those skilled in the artsuch as adhesives. Such a second body portion 120 is constituted so asto carry one or more treatment mediums, for example analgesics, anantibiotic or a medicament or medium used for treating dry eyecondition, and provide a delivery vehicle or structure, such as a matrixor medium, that is constituted so it releasably retains the one or moretreatment mediums therein so the medium can be released there from underpredetermined conditions. Such releasably retaining includes but is tolimited to encapsulation of the treatment medium(s) within the structurecomprising the delivery vehicle or structure. It also is contemplatedthat the second body portion 120 can comprise a medium or material, forexample a polymer, that is formed, cured or otherwise appropriatelyprocessed such that it is bonded to the first body portion second end114 a-c, as a result of such forming, curing, polymerizing orprocessing.

Preferably, the delivery vehicle or structure is further constituted sothe treatment medium being releasably retained therein is released fromthe vehicle or structure at a controlled or essentially controlledprocess, more preferably releasing the treatment medium withoutsignificantly affecting the properties or activity of the treatmentmedium's active element(s) or constituents. In illustrative exemplaryembodiment, the one or more treatment mediums are released to the fluidfound on the eye, more specifically the tears secreted by the bodilystructures and glands making up a mammalian eye. In particularembodiment, the delivery vehicle or structure also is constituted so itis characterized as being generally biocompatible, non-toxic andnon-sensitizing.

In an illustrative exemplary embodiment, the second body portion 120 canbe constituted of a biodegradable polymers containing microparticles ofthe treatment medium such as that described for example, in U.S. Pat.No. 5,098,443 the teachings of which are incorporated herein byreference. In another exemplary embodiment, and with reference to FIGS.2C, 4, the second body portion 120 c is formed so as to include one ormore compartments or chambers 122 therein, where each of the one or morecompartments includes one or more treatment mediums (e.g., differenttreatment mediums 126 x, 126 y, 126 z disposed in different chambers122).

The surrounding part 124 of the second body portion 120 c can comprise apolymeric material whereby the treatment medium is slowly releasedthereof by osmosis as suggested in U.S. Pat. No. 5,098,443. In analternative embodiment, the second end portion 120 can be configured andarranged so as to function much like membrane diffusion drug deliverysystem such as that described in U.S. Pat. No. 5,378,475 or U.S. Pat.No. 5,466,233 the teachings of which are incorporated herein byreference. For example, the surrounding part 124 would comprise twocoatings with different permeabilities, whereby the treatment mediumdiffuses through a small opening in one of these coatings achievingnear-order release kinetics.

In yet another embodiment, the second body portion including the chamber122 and the surrounding portion 124 thereof are configurable so as toessentially form any of a number of biocompatible capsules as is knownin the art that are suitable for delivery of the therapeutic medium. Inexemplary embodiments, the chamber 122 corresponds to the compartment ofthe biocompatible polymer capsules that contains the treatment medium,either suspended in a liquid medium or immobilized within abiocompatible matrix, and (b) the surrounding part 124 corresponds tothe surrounding jacket that comprises a membrane that is biocompatibleand permits diffusion of the treatment medium (e.g., drugs,therapeutics, medicaments such as proteins, cells or small moleculepharmaceuticals, or the like) to the tissues of the eye. As indicatedherein, the chamber 122 also can be constituted so it includes abiocompatible matrix of a hydrogel or other biocompatible matrixmaterial that stabilizes the position of the therapeutic medium. Thesurrounding part 124 or surrounding jacket may be manufactured fromvarious polymers and polymer blends including polyacrylates (includingacrylic copolymers), polyvinylidenes, polyvinyl chloride copolymers,polyurethanes, polystyrenes, polyamides, cellulose acetates, cellulosenitrates, polysulfones (including polyether sulfones), polyphosphazenes,polyacrylonitriles, poly(acrylonitrile/covinyl chloride), as well asderivatives, copolymers, and mixtures thereof.

Now referring also to FIG. 2B, the second body portion 120 b isconfigurable so as to present any of a number of surface arrangements orprofiles that are otherwise appropriate for the intended use. As shownin FIG. 2A, the second body portion 120 is configurable so as to presenta cylindrical profile with an arcuate or generally hemispherical end.Alternatively, and as shown in FIG. 2B, the end profile of the secondbody portion 120 b while arcuate is arranged so as to be concave ordished like, whereby for example, the fluid in the eye can repose andremain in contact with the second body portion 120 b. In more particularembodiments, the second body portion 120 also is configured and shapedso as to present a non-traumatic end profile so as to minimize traumaand or injury to tissues or body features (e.g., eyelids), that can comein contact with the second body portion 120 when the delivery device isremovably secured within the bodily opening (e.g., punctum).

In further embodiments, the second body portion 120 is configurable so aportion thereof comprises a non-linear shaped member have multiple turnsor angles, for example at least two, three, four, five, six, seven,right, nine or ten separate deviations from a linear path. Such anon-linear shaped member comprises a coil shape, random curled shapes, azigzag shape, a “J” shape, a “C” shape and the like.

Although the first body portion 110 is generally illustrated in FIGS.2A,B as a extending along a long or longitudinal axis, this shall not beconstrued as limiting a delivery device of the present invention to theillustrated structure. It is contemplated and within the scope of thepresent invention for the first body portion to be configured andarranged within any of a number of configurations and shapes known tothose skilled in the art that are consistent with the intended use andfunction of the present invention.

In the embodiment shown in FIG. 2C, the first body portion 110 c isconfigured so as to comprise a continuous coil structure made up of aplurality of coil turns 113 that curl about the longitudinal axis of thefirst body portion. Such a coiled first body portion 110 c also isconfigured and arranged so that the characteristics and properties(e.g., spring constant) of the coiled structure is such that the coiledfirst body portion has sufficient axial and/or radial rigidity so thatit can be inserted into the opening without significant bending ordeformation of the coiled structure during such insertion, therebyminimizing trauma or significant injury to the tissues at the entrysite. In addition, the coiled structure also has sufficient axial and/orradial rigidity to also allow the coiled first body portion 110 c to beretracted or removed from the opening while also minimizing trauma orsignificant injury to the tissues during such retraction. As alsoillustrated in FIG. 2C, the second body portion 120 c is attached,secured, bonded or applied to an end 114 of the coiled first bodyportion 110 c using any of a number of techniques known to those skilledin the art.

FIG. 2D shows a delivery device 100 d formed in accordance with anotherembodiment of the present invention. Delivery device 100 d comprises afirst body portion 110 d in the form of a stent 117 having a passagewayor lumen 119, and a second body portion 120 d in the form of acompressed drug pellet. As described earlier, the different forms of thefirst body portion and second body portion may be used with each otherin any suitable combination for the particular application; for example,a first body portion comprising a stent may be combined with a secondbody portion in the form of a coating (i.e. the coating may be appliedto an end of the stent).

In further refinement of the present invention, the first and secondbody portions 110, 120 are configured and arranged so either of the twoportion or the combination of the two portions create a delivery device100 that occludes, blocks or plugs the body opening (e.g., punctum) inwhich at least a part of the first body portion 110 is inserted into,thereby also occluding, blocking or plugging any passage, duct or otherbodily feature to which the opening is fluidly coupled to. In this way,the treatment medium is retained in proximity to the external surface(s)of the eye and is essentially prevented from leaving the treatment sitevia the blocked passage or duct. Alternatively, the first and secondbody portions 110, 120 are configured and arranged such that the secondbody portions rests on the punctum and the device 100 does not occludethe punctum.

Thus, the treatment medium being delivered by the delivery device 100 ofthe present invention is not diluted or reduced because of drainage fromthe eye through the nasolacrimal duct as is experienced or seen with theuse of conventional techniques for the topical administration oftreatment mediums including therapeutics and medicaments. Thus, incomparison to conventional techniques the amount of the treatment mediumthat is available for treatment is not also thereby reduced.Consequently, the dosage or amount of treatment medium to be releasedfrom a delivery device 100 of the present can be reduced as compared toconventional devices or conventional techniques thereby also reducingthe potential or risk of unwanted systemic side effects. Further, theincreased retention time of the treatment medium when using the deliverydevice of the present invention as compared to that seen usingconventional topical administration techniques and/or devices allows amore effective treatment protocol to be established.

In addition, the delivery device of the present invention overcomes anumber of the shortcomings of conventional topical insets. As indicatedherein, such topical inserts are such that they are easily removed fromthe eye and also require action on the part of the patient toperiodically replace the insert as it is used up as well as when theinsert falls out. In contrast, the delivery device 100 of the presentinvention is configured and arranged so it remains secured within thebody opening (e.g., punctum) during normal bodily processes andfunctions.

Also, because the treatment medium available for treatment using thedelivery device of the present invention is increased as compared tothat available when using prior art devices or inserts, the periodicityof replacement is decreased (i.e., time between removal and replacementincreased). Thus, it becomes possible when using a delivery device ofthe present invention for the process of removing an old delivery deviceand inserting a new delivery device to be performed by trained medicalpersonnel instead of the patient.

In the foregoing discussion the delivery device 100 of the presentinvention is described as occluding the passage or duct associated withthe opening in which the deliver device is inserted. It also iscontemplated and thus within the scope of the present invention,however, for the first and second body portions 110, 120 to be furtherconfigured and arranged so that a lumen or passage is created within thedeliver device that in effect re-opens the occluded passage or duct, atleast to some degree, after the treatment medium is spent. In this way,for example, the punctum is effectively re-opened thereby allowingdrainage of fluid to the tear ducts 6 (FIG. 6) thus allowing the patientto regain drainage function to some extent without requiring the patientto return to the medical personnel for removal of the delivery deviceimmediately or shortly after completion of the treatment process.

In further embodiments, the treatment medium comprises mediums or agentsin what ever form that are useable in connection with, but not limitedto, the treatment of a wide range of disorders, diseases, and/orphysiological problems of a mammalian eye. Such treatment mediums of thepresent invention in what ever form useable in connection with surgicalprocedures. Such treatment mediums include but are not limited totherapeutics and medicaments. Exemplary therapeutic mediums include, butare not limited to, thrombin inhibitors; antithrombogenic agents;thrombolytic agents; fibrinolytic agents; vasospasm inhibitors; calciumchannel blockers; vasodilators; antihypertensive agents; antimicrobialagents, such as antibiotics (such as tetracycline, chlortetracycline,bacitracin, neomycin, polymyxin, gramicidin, cephalexin,oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin,gentamycin, erythromycin, penicillin, sulfonamides, sulfadiazine,sulfacetamide, sulfamethizole, sulfisoxazole, nitrofurazone, sodiumpropionate), antifungals (such as amphotericin B and miconazole), andantivirals (such as idoxuridine trifluorothymidine, acyclovir,gancyclovir, interferon); inhibitors of surface glycoprotein receptors;antiplatelet agents; antimitotics; microtubule inhibitors;anti-secretory agents; active inhibitors; remodeling inhibitors;antisense nucleotides; anti-metabolites; antiproliferatives (includingantiangiogenesis agents); anticancer chemotherapeutic agents;anti-inflammatories (such as hydrocortisone, hydrocortisone acetate,dexamethasone 21-phosphate, fluocinolone, medrysone, methylprednisolone,prednisolone 21-phosphate, prednisolone acetate, fluoromethalone,betamethasone, triamcinolone, triamcinolone acetonide); non-steroidalanti-inflammatories (such as salicylate, indomethacin, ibuprofen,diclofenac, flurbiprofen, piroxicam); antiallergenics (such as sodiumchromoglycate, antazoline, methapyriline, chlorpheniramine, cetrizine,pyrilamine, prophenpyridamine); anti-proliferative agents (such as1,3-cis retinoic acid); decongestants (such as phenylephrine,naphazoline, tetrahydrazoline); miotics and anti-cholinesterase (such aspilocarpine, salicylate, carbachol, acetylcholine chloride,physostigmine, eserine, diisopropyl fluorophosphate, phospholine iodine,demecarium bromide); antineoplastics (such as carmustine, cisplatin,fluorouracil); immunological drugs (such as vaccines and immunestimulants); hormonal agents (such as estrogens, estradiol,progestational, progesterone, insulin, calcitonin, parathyroid hormone,peptide and vasopressin hypothalamus releasing factor);immunosuppressive agents, growth hormone antagonists, growth factors(such as epidermal growth factor, fibroblast growth factor, plateletderived growth factor, transforming growth factor beta, somatotropin,fibronectin); inhibitors of angiogenesis (such as angiostatin,anecortave acetate, thrombospondin, anti-VEGF antibody); dopamineagonists; radiotherapeutic agents; peptides; proteins; enzymes;extracellular matrix components; ACE inhibitors; free radicalscavengers; chelators; antioxidants; anti-polymerases; photodynamictherapy agents; gene therapy agents; and other therapeutic agents suchas prostaglandins, antiprostaglandins, prostaglandin precursors, and thelike.

Antiproliferatives include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art thatinhibit the proliferation of cells Such compounds, agents, therapeuticmediums or drugs include, but are not limited to, 5-fluorouracil, taxol,rapamycin, mitomycin C and cisplatin.

Neuroprotectives include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art thatguard or protect against neurotoxicity; the quality of exerting adestructive or poisonous effect upon nerve tissue. Such compounds,agents, therapeutic mediums or drugs include, but are not limited to,lubezole.

Anti-inflammatories include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art, eithersteroidal or non-steroidal, and generally characterized has having theproperty of counteracting or suppressing the inflammatory process.Non-steroidal inflammatory drugs or compounds comprise a class of drugsthat shares the property of being analgesic, antipyretic andanti-inflammatory by way of interfering with the synthesis ofprostaglandins. Such non-steroidal anti-inflammatories include, but arenot limited to, indomethacin, ibuprofen, naxopren, piroxicam andnabumetone. Such anti-inflammatory steroids contemplated for use in themethodology of the present invention, include triamcinolone acetonide(generic name) and corticosteroids that include, for example,triamcinolone, dexamethasone, fluocinolone, cortisone, prednisolone,flumetholone, and derivatives thereof (See also U.S. Pat. No. 5,770,589,the teachings of which are incorporated herein by reference).

As is known to those skilled in the art, growth factors is a collectiveterm originally used to refer to substances that promote cell growth andis now loosely used to describe molecules that function as growthstimulators (mitogens) but also as growth inhibitors (sometimes referredto as negative growth factors), factors that stimulate cell migration,or as chemotactic agents or inhibit cell migration or invasion of tumorcells, factors that modulate differentiated functions of cells, factorsinvolved in apoptosis, factors involved in angiogenesis, or factors thatpromote survival of cells without influencing growth anddifferentiation. In the present invention, such growth factors include,but are not limited to, pigment epithelium derived factor and basicfibroblast growth factor.

As is known to those skilled in the art, neurotropic factors is ageneral term used to describe growth factors and cytokines that canenhance neuronal survival and axonal growth and that regulate synapticdevelopment and plasticity in the nervous system. In the presentinvention, such growth factors include, but are not limited to, ciliaryneurotrophic factors and brain-derived neurotrophic factors.

Antiangiogenics include any of a number of compounds, agents,therapeutic mediums or drugs known to those skilled in the art thatinhibit the growth and production of blood vessels, includingcapillaries. Such compounds, agents, therapeutic mediums or drugsinclude, but are not limited to, anecortave acetate and anti VEGF agentsor the activity sites of anti VEGF agents. Anti VEGF agents include, butare not limited to, Macugen, Lucentis, Avastin, Squalamine, and Kenalog.

Thrombolytics, as is known to those skilled in the art include any of anumber of compounds, agents, therapeutic mediums or drugs that dissolveblot clots, or dissolve or split up a thrombus. Such thrombolyticsinclude, but are not limited to, streptokinase, tissue plasminogenactivator or TPA and urokinase.

Such treatment mediums also include fluticasone.

The treatment medium including therapeutics being delivered oradministered is in any of a number of formulations including, fluidsolutions, solids and/or sustained release formulations or devices. Infurther embodiments, the sustained releases devices comprising saidanother portion of the delivery device of the present invention include,but are not limited to those having the following characteristics;flexible rods, thin films, foldable discs, biodegradable polymers withthe therapeutic medium (e.g., drug) embedded within, bioerodablematerials, drug eluting polymer coatings over a rigid scaffold,compressed drug “pellets” or a therapeutic medium encapsulated in asemi-permeable membrane. Also, some characteristic formulations fordelivery of the treatment medium include, but are not limited to,injectable hydrogels, cyclodextrin “solubilized” and micronizedsolutions.

The use of any of the herein described delivery devices 100, 100 b, 100c, 100 d of the present invention as well as the methods for treating awide range of disorders and diseases of the eye as well as pre-operativeand post-operative administration of a wide range of therapeutics andtreatments mediums and/or agents can be understood from the followingdiscussion with reference to FIGS. 5, 6. The methodologies of thepresent invention shall be understood to include, but not limited to,(a) pre- and post-operative treatments associated with Lasik, cataractor refractive procedures or glaucoma procedures as is known to thoseskilled in the art including but not limited to the administration ofanti-inflammatory therapeutics (e.g., steroidal anti-inflammatory drugs)and anti-infective therapeutics, including antibiotics; (b) postoperative treatments and delivery of topical drugs associated with thepost operative management of corneal transplants; (c) treatment ofcomeal disorders such as corneal melts by topical administration ofdrugs; (d) treatment of inflammatory disorders or infectious problems ofthe eye (e.g., conjunctivitis) by topical administration ofanti-inflammatory therapeutics or anti-infective therapeutics; and/or(e) treatment of dry eye over a short or long period of time withartificial tears, Restasis, allegran or other agents known to thoseskilled in the art as well post-operative treatments in which desiredlevels of moisture are to be maintained (e.g., post-operative associatedwith cataract procedures).

Reference also should be made to the foregoing discussion for FIGS. 2-4for features of a delivery device of the present invention not otherwiseshown in FIGS. 5 and 6. In addition, while reference is made in thefollowing discussion to the delivery device 100 shown in FIG. 2A, thisshall not be construed as limiting the methodologies of the presentinvention to this delivery device as such methodologies are usably withany of the delivery devices described herein as well as any embodimentsand aspect thereof also described herein or reasonably inferable fromthe teachings provided herein.

Prior to insertion, the medical personnel would remove the treatmentdelivery device 100 from any protective packaging and ready the deliverydevice for insertion into the bodily opening, in the illustratedembodiment the punctum 4. In addition, the medical personnel (e.g.,surgeon) would take those other actions required to make the punctum 4ready for such insertion.

Thereafter the medical personnel would grasp the delivery device 100using any of a number of devices known to those skilled in the art suchas for example forceps or clamps. The medical personnel would thenmanipulate the delivery device so the first end 112 of the first bodyportion 110 is proximal the punctum 4 and then insert such first endinto the opening of the punctum. The medical personnel would continue toinsert the first body portion 110 into the punctum so the deliverydevice is secured within the punctum and retained by the associatedlacrimal canaliculus as well as so the second body portion 120 isappropriately positioned to minimize trauma and/or injury to the tissuesof the eye after such insertion is completed.

After the expiration of a predetermined period of time, the medicalpersonnel would assess the progress of treatment as well as theassessing any post-operative conditions of the eye. If further treatmentis needed, or the type and/or quantity of treatment medium beingdispensed needs to be adjusted, the medical personnel would extract thepresently inserted treatment medium delivery device 100 from the punctumand insert another treatment delivery device therein, which device isconstituted so as to be capable of dispensing the desired type and/oramount of treatment medium. If the treatment process is complete, thenthe medical personnel would remove the presently inserted deliverydevice 100 from the punctum.

Although a preferred embodiment of the invention has been describedusing specific terms, such description is for illustrative purposesonly, and it is to be understood that changes and variations may be madewithout departing from the spirit or scope of the following claims.

All patents, published patent applications and other referencesdisclosed herein are hereby expressly incorporated by reference in theirentireties by reference.

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents of the specificembodiments of the invention described herein. Such equivalents areintended to be encompassed by the following claims.

What is claimed is:
 1. A device for delivering a treatment medium to aneye, comprising: a first body portion and a second body portion; whereinthe first body portion is configured and arranged to be removablysecured within a natural opening comprising a single punctum of the eyeand wherein the first body portion comprises a lumen; and wherein thesecond body portion is configured to release the treatment medium to theeye, wherein the treatment medium is immobilized in a biocompatiblematrix; and wherein the delivery device is configured and arranged suchthat when at least a part of the first body portion is removablyinserted into the punctum, the device occludes or plugs the punctum. 2.The device of claim 1, wherein the treatment medium comprises aprostaglandin.
 3. The device of claim 1, wherein the first body portionincludes a plug type member, one end of which is configured and arrangedso as to be removably secured within the punctum.
 4. The device of claim1, wherein the first body portion includes a stent.
 5. The device ofclaim 1, wherein the first body portion includes a cylindrical plugmember.
 6. The device of claim 1, wherein the treatment medium isdelivered in a controllable manner over a predetermined time perioddirectly to the eye.
 7. The device of claim 1, wherein the treatmentmedium is retained in proximity to the external surface of the eye andis prevented from leaving the treatment site via the blocked punctum. 8.The device of claim 1, wherein the treatment medium is selected from thegroup consisting of thrombin inhibitors; antithrombogenic agents;thrombolytic agents; fibrinolytic agents; vasospasm inhibitors; calciumchannel blockers; vasodilators; antihypertensive agents; antimicrobialagents; inhibitors of surface glycoprotein receptors; antiplateletagents; antimitotics; microtubule inhibitors; anti-secretory agents;active inhibitors; remodeling inhibitors; antisense nucleotides;anti-metabolites; antiproliferatives; anticancer chemotherapeuticagents; anti-inflammatories; non-steroidal anti-inflammatories;antiallergenics; antiproliferative agents; decongestants; miotics andanticholinesterase; antineoplastics; immunological drugs; hormonalagents; immunosuppressive agents; growth hormone antagonists; growthfactors; inhibitors of angiogenesis; dopamine agonists; radiotherapeuticagents; peptides; proteins; enzymes; extracellular matrix components;ACE inhibitors; free radical scavengers; chelators; antioxidants;anti-polymerases; photodynamic therapy agents; gene therapy agents;prostaglandins; antiprostaglandins; prostaglandin precursors andcombinations thereof.
 9. The device of claim 1, wherein the first bodyportion comprises a first end that is configured to facilitate insertionof the first body portion into the punctum.
 10. The device of claim 1,wherein the first body portion comprises a second end that is configuredto form a support for the second body portion.
 11. The device of claim1, wherein the first body portion extends along a longitudinal axis. 12.The device of claim 1, wherein the second portion is shaped to at leastpartially rest upon the punctum when the first portion is retained bythe lacrimal canaliculus.
 13. The device of claim 1, wherein the secondportion includes sustained release means for releasing the treatmentmedium over a predetermined period of time.
 14. The device of claim 1,wherein the biocompatible matrix is a biodegradable or bioerodiblematerial.
 15. The device of claim 1, wherein the second portion isbonded to the first portion via a forming, curing, or polymerizationprocess.
 16. A method for treating an eye, comprising: providing adelivery device comprising a treatment medium, wherein the devicecomprises a first body portion and a second body portion; wherein thefirst body portion is configured and arranged to be removably securedwithin a natural opening comprising a single punctum of the eye andwherein the first body portion comprises a lumen; and wherein the secondbody portion is configured to release the treatment medium to the eye,wherein the treatment medium is immobilized in a biocompatible matrix;and wherein the delivery device is configured and arranged such thatwhen at least a part of the first body portion is removably insertedinto the punctum, the device occludes or plugs the punctum; andinserting the first portion of the delivery device into a punctum of theeye such that the first portion is retained by a single lacrimalcanaliculus of the eye and the second portion of the delivery device isadjacent to an external surface of the eye.
 17. The method of claim 16,comprising eluting or diffusing the treatment medium to the eye.
 18. Themethod of claim 16, wherein the treatment medium is formulated as asustained release formulation.
 19. The method of claim 16, wherein thetreatment medium is a treatment for pre- and post-operative inflammationor pain, glaucoma, inflammation, infections, or dry eye.